130: Clinical Outcomes of Carfilzomib-based Chemotherapy by Relative Dose Intensity in Patients with Relapsed or Refractory Multiple Myeloma

Statement of Purpose, Innovation or Hypothesis: Multiple myeloma is a hematologic disorder characterized by abnormal proliferation of plasma cells in the bone marrow. The National Comprehensive Cancer Network guidelines version 1.2024 recommend carfilzomib, lenalidomide, and dexamethasone combination therapy (KRd) as the standard treatment for relapsed or refractory multiple myeloma. For patients with compromised overall performance or frailty, a two-drug regimen with carfilzomib and dexamethasone (Kd) is suggested, along with dose adjustments based on activity level and age. In the treatment of multiple myeloma, which accounts for the majority of elderly patients, weakness and poor activity performance are generally known to increase the frequency of severe side effects in patients, and in practice, dose reductions are frequent due to adverse drug reactions during anticancer therapy for multiple myeloma. This study evaluated the dosage intensity of carfilzomib-based therapy, its therapeutic effects, and safety in a retrospective cohort of patients treated at Bundang Seoul National University Hospital from May 1, 2017, to November 30, 2022.

Description of Methods & Materials: The study included patients aged 19 and above with relapsed or refractory multiple myeloma. Treatment outcomes, including overall response rate, progression-free survival (PFS), and overall survival (OS), were assessed. Cox proportional hazard models were employed to analyze factors influencing survival.

Data & Results: The study included 126 eligible patients, with 85 in the KRd group and 41 in the Kd group. The median follow-up duration was 18.7 months (range 0.3-63.2). The relative dose intensity (RDI) was 0.85±0.15 for the KRd group and 0.66±0.22 for the Kd group. The KRd group showed an overall response rate of 88.0%, a median PFS of 16.8 months (95% CI 13.6-26.5), and an OS of 33.1 months (95% CI 27.4-43.2). The Kd group exhibited an overall response rate of 57.9%, a median PFS of 6.4 months (95% CI 3.0-9.8), and an OS of 26.4 months (95% CI 11.5-39.8). As a result of multivariate analysis, PFS was found to be reduced when RDI was less than 0.7 (HR 2.00, 95% CI 1.09-3.65, p=0.025) and Revised International Staging System(R-ISS) stage III (HR 4.11, 95% CI 2.24-7.54, p < 0.001) and three or more chemotherapy were previously administered (HR 2.53, 95% CI 1.30-4.90, p=0.006). OS was confirmed to be reduced significantly in non-IgG type M protein (HR 1.99, 95% CI 1.09-3.62, p=0.024), R-ISS stage III (HR 2.69, 95% CI 1.32-5.47, p=0.006), cytogenetic/FISH high risk (HR 1.99, 95% CI 1.04-3.81, p=0.039). Safety analysis identified adverse events using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Among all patients, 98.4% reported adverse events, with both groups experiencing common side effects such as hematologic toxicity and infections, fatigue, and peripheral neuropathy. Grade 3 or higher adverse events occurred in 72.9% of the KRd group and 73.2% of the Kd group.

Interpretation, Conclusion or Significance: In conclusion, the study found that an RDI of 0.7 or less in carfilzomib-based therapy up to two cycles impacted progression-free survival. Vigilance is necessary for cardiovascular and hematologic side effects during treatment.

Disclosures: There are no financial conflicts of interest to disclose

Citations/References: 1. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial, Meletios A Dimopoulos, Hartmut et al., Lancet Oncol 2017; 18: 1327–37
2. Jakubowiak, A. J. (2014). Evolution of carfilzomib dose and schedule in patients with multiple myeloma: a historical overview. Cancer treatment reviews, 40(6), 781-790.

Additional Information/Authors: Soo-Mee Bang, Division of Hematology-Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital